Methoxyethoxymethyl esters

Conversion of MEM ethers to esters. 2-Methoxyethoxymethyl (MEM) ethers are converted into carboxylic esters by reaction with an anhydride in the presence of FeCl3 (0.4 equiv.) (equation I). Selective cleavage is possible in the presence of a benzyl ether but not in the presence of a f-butyl ether. Aromatic rings, if present, can undergo acylation. 

The norephedrine-derived Masamune asymmetric aldol reaction was utilized in the total synthesis of (+)-testudinariol A (12), a triterpene marine natural product that possesses a highly functionalized cyclopentanol framework with four contiguous stereocenters appended to a central 3-alkylidene tetrahydropyran6 (Scheme 2.2f). The norephedrine-derived ester 13 was enolized with dicyclo-hexylboron triflate and triethylamine in dichloromethane and then treated with 3-benzyloxypropanal to afford the aldol adduct (14) as a 97 3 mixture of anti/syn diastereomers in 72% yield. Diastereoselectivity within the anti -manifold was 90 10. Protection of alcohol as the methoxyethoxymethyl (MEM) ether followed by conversion of the ester to an aldehyde by LiAlELt reduction and subsequent Swem oxidation gave the aldehyde 16 in 64% yield over three steps. 

Cleavage of MEM ethers. 2-Methoxyethoxymethyl (MEM) ethers are cleaved by NaI/ClSi(CH,)3 in CHjCN at —20 or 25° in moderate to high yield, lodotrimethylsilane (commercial) is less effective. Fairly selective cleavage of MEM ethers is possible in the presence of lactones, methyl or benzyl ethers, and methyl esters. 

Reduction of methoxyethoxymethyl MEM) esters. MEM esters are more easily reduced by lithium triethylborohydride than other esters. Selective reduction of a less hindered MEM ester is also possible. ... 

Ester cleavage. The AlClj-PhNMe2 combination is a versatile reagent to cleave methyl, benzyl, methoxymethyl, methylthiomethyl, methoxyethoxymethyl, and /3-(trimethylsilyl)ethoxymethyl esters at room temperature. 

Carboxylic acids, their esters, and amides are usually resistant to sodium borohydride reduction, whereas carboxylic acid chlorides may be reduced in inert solvents to give alcohols. Where this proves unsatisfactory a new alternative procedure for acid chloride reduction in ether solution involves sodium borohydride adsorbed on alumina. Other recently published borohydride reductions of acid derivatives to primary alcohols include those of the 1-succinimidyl esters (8)" and the N-nitroso-amides (9). 2-Methoxyethoxymethyl (MEM) esters have the possibility of co-ordinating the metal cation of complex hydrides at the MEM group, and hence of activating the carbonyl group towards reduction by intramolecular hydride delivery. The selective reduction of the less hindered ester group in the bis-MEM ester (10) to give (11) illustrates this idea. 

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